In early postnatal life there are changes in hemoglobin-oxygen affinity and blood hemoglobin concentration in all species which have been examined. The molecular events which initiate these changes are unknown. We have selected two species, canine and caprine, which differ in their apparent mechanisms for modulation of hemoglobin-oxygen affinity. The oxygen affinity of whole blood, the concentrations of possible effectors and the activities of the carbonic anhydrase isozymes and the enzymes diphosphoglycerate mutase and disphosphoglycerate phosphatase will be determined during fetal and early postnatal life. We will also monitor any major changes in carbon dioxide transport. Chemical analyses will be used to confirm the identify of fetal and adult canine hemoglobin. Statistical correlations between oxygen affinity and effector concentrations or enzyme activity will be sought. Positive or negative correlations will be tested in vitro by examining the change in oxygen affinity of isolated hemoglobin due to addition of the apparently significant effector. Within this framework we will then confirm the in vivo significance by suitable experimental manipulation. The available possibilities include a) transfusion of newborn dogs or goats with compatible blood from littermates, b) blood loss anemia, c) exposure to hopoxic environment, d) modification of red cell diphosphoglycerate concentrations.